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Study in HFpEF Patients to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03682497
Recruitment Status : Terminated (Attendance at study sites carries risk of COVID-19 infection. Non-attendance at planned study site visits has unacceptable study related patient safety risk.)
First Posted : September 24, 2018
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a Phase I, Multicentre study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] during 28 days in Patients with HFmrEF or HFpEF and eGFR in the range of ≥40 and ≤70 mL/min/1.73m2.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: AZD9977 Drug: Spironolactone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Randomized, Parallel Group, Multicentre Study to Compare the Effect of AZD9977 and Spironolactone on Serum Potassium [sK+] During 28 Days in Patients With HFmrEF or HFpEF and eGFR in the Range of ≥40 and ≤70 mL/Min/1.73m2.
Actual Study Start Date : November 1, 2018
Actual Primary Completion Date : March 31, 2020
Actual Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Spironolactone
Spironolactone treatment for 28 days
Drug: Spironolactone
Spironolactone tablets taken orally for 28 days.

Experimental: AZD9977
AZD9977 treatment for 28 days
Drug: AZD9977
AZD9977 capsules taken orally for 28 days.




Primary Outcome Measures :
  1. Relative change (%) from baseline in serum potassium [ Time Frame: Measurements on day 1, 7, 14, 21 and 28 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 28. ]
    To compare the effect of AZD9977 with spironolactone on serum potassium (sK+)


Secondary Outcome Measures :
  1. Plasma trough concentrations (Ctrough) values of spironolactone and AZD9977 [ Time Frame: PK samples will be taken (within 60 min prior to dose) at day 1, 7, 14, 21 and 28. ]
    To evaluate the pharmacokinetics (PK) of AZD9977 and spironolactone

  2. Relative change (%) from baseline in serum potassium [ Time Frame: Measurements on day 1, 7 and 14 will be used. The primary comparison between Spironolactone and AZD9977 will be done at day 14. ]
    To compare the effects of AZD9977 with spironolactone on serum potassium at Day 14.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptoms and signs consistent with a diagnosis of heart failure (HF)
  • Left ventricular ejection fraction (LVEF) ≥40% by transthoracic echocardiography within the past 12 months
  • Plasma NT-proBNP level ≥125 pg/ml (≥ 600pg/mL if patient has persistent or permanent atrial fibrillation, atrial flutter, or atrial tachycardia)
  • Estimated glomerular filtration rate (eGFR) ≥40 and ≤70ml/min/1.73m2 (by CKD-EPI formula).
  • Baseline serum potassium (sK+) level ≥3.5 and ≤4.8mmol/l.
  • Stable doses of the following medications at baseline for at least 4 weeks prior to randomisation:

Angiotensin receptor blocker (ARB) or Angiotensin converting enzyme inhibitor (ACEi) Loop diuretic (up to a 120mg furosemide dose or equivalent

Exclusion Criteria:

  • Patients with documented LVEF <40% at any time (i.e. patients with previously impaired LVEF that has now improved are not permitted).
  • Patients experiencing acute decompensation of heart failure requiring hospital admission or escalation in therapy.
  • Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy in judgment of Investigator).
  • Hyponatraemia, defined as serum Na+ <135 mmol/L at the time of enrollment.
  • Persistent resting sinus tachycardia >110 bpm or sinus bradycardia <45bpm.
  • Systolic blood pressure (BP) <110mmHg or >180mmHg.
  • Diastolic BP <60 mmHg or >100 mmHg.
  • Patients previously intolerant to MRA (e.g. spironolactone or eplerenone) for any reason.
  • Medical conditions associated with development of hyperkalaemia (e.g. Addison's disease).
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN).
  • Patients who have been taking an MR antagonist within 1 month prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03682497


Locations
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Bulgaria
Research Site
Plovdiv, Bulgaria, 4002
Research Site
Sofia, Bulgaria, 1309
Research Site
Sofia, Bulgaria, 1784
Czechia
Research Site
Brandys nad Labem, Czechia, 250 01
Research Site
Ceska Lipa, Czechia, 470 77
Research Site
Jaromer, Czechia, 551 01
Research Site
Louny, Czechia, 440 01
Research Site
Pardubice, Czechia, 530 02
Research Site
Praha, Czechia, 130 00
Research Site
Praha, Czechia, 140 59
Poland
Research Site
Katowice, Poland, 40-081
Research Site
Kraków, Poland, 31-202
Research Site
Legnica, Poland, 59-220
Research Site
Warszawa, Poland, 02-097
Research Site
Wrocław, Poland, 50-981
United Kingdom
Research Site
Hull, United Kingdom, HU3 2JZ
Research Site
Leicester, United Kingdom, LE3 9PQ
Research Site
Sheffield, United Kingdom, S5 7AU
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03682497    
Other Study ID Numbers: D6401C00004
First Posted: September 24, 2018    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Heart failure.
Oral selective mineralocorticoid receptor modulator.
Heart failure with preserved ejection fraction (HFpEF).
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents